This invention relates to the preparation of test samples for automatic analysis in a sample analysis system and more particularly to a novel apparatus and method for diluting a test sample before it is combined with a reagent in a sample analysis system.
In known automatic sampling systems, such as shown in U.S. Pat. No. 5,268,147, test samples of blood or serum are permitted to react with one or more reagents to produce measurable test results that are the basis for an analytical determination of blood characteristics. Known sampling systems often include a pipette or sampling probe to aspirate a predetermined volume of test sample from a container such as a tube or cuvette. The aspirated test sample is usually mixed with a predetermined volume of diluent before the test sample is added to a reagent. Dilution of the test sample helps control a test reaction when the test sample is combined with a reagent.
One known system for diluting a fluid sample, indicated as prior art in FIGS. 1-3, includes an aspiration probe with two continuous communicable interior sections of different diametrical magnitude. A first interior section of the aspiration probe is proximate an inlet opening, and a second interior section of larger diametrical magnitude is located beyond the first section. Both interior sections of the probe are generally disposed along a vertical axis.
Predetermined amounts of fluid sample and diluent are sequentially aspirated into the first interior section, as detailed in U.S. Pat. No. 5,773,305. The fluid sample and diluent are then drawn further into the probe from the first interior section to the second interior section.
The fluid sample and diluent, when located in the second interior section, are moved back and forth along a substantially vertical axis a predetermined number of times by alternate vacuum and pressure forces. Repeated back and forth movement of the fluid sample and diluent in the second interior section of the probe provides substantially uniform mixing or dilution of the fluid sample.
In many instances an oil coating is provided along the inside surface of the probe and the mixing chamber to facilitate flow and reduce carry over of sample or diluent to a next use of the device. Applicants have found that an oil filled aspiration line and mixing chamber wherein the oil can be withdrawn in the hydraulic line by a pump and later reintroduced into the hydraulic line during dispensation of a diluted test sample serves to minimize carryover.
It is thus desirable to provide a method and apparatus for diluting a test sample and diluent which minimizes carryover of sample or diluent to a next use of an aspiration device.
Among the several objects of the invention may be noted the provision of a novel method and apparatus for diluting a test sample, a novel method and apparatus for diluting a test sample wherein a selected amount of test sample and a selected amount of diluent are aspirated and mixed together in an aspiration line, a novel method and apparatus for diluting a test sample that is separated from diluent by an air bubble which does not result in inclusion of the air bubble in the diluted test sample, a novel method and apparatus for mixing test sample with diluent that permits use of an oil filled line prior to sample aspiration and during dispensation of a diluted test sample.
Other objects and features of the invention will be in part apparent and in part pointed out hereinafter.
In accordance with the invention the sample dilution module includes an aspiration probe for separately aspirating a first predetermined amount of test sample from a test sample container and a second predetermined amount of diluent from a diluent container. The aspiration probe has an inlet opening and an aspiration path extending from the inlet opening along a substantially vertical axis.
A mixing section is joined to the aspiration probe and has a mixing chamber communicable with the aspiration path of the aspiration probe. The mixing chamber is inclined approximately 5 to 45 degrees below the horizontal axis, preferably 15 degrees below the horizontal axis. The mixing chamber is without any mixing element and is of a greater diameter than the diameter of the aspiration path. In a preferred embodiment of the invention the mixing section and the aspiration probe are formed as a one-piece structure.
The mixing section communicates with pumping means for drawing the test sample and diluent from the vertical aspiration path in the aspiration probe to the mixing chamber. The pumping means can also alternately exert suction and pressure forces on the test sample and diluent in the mixing chamber to move the test sample and diluent back and forth in the mixing chamber. Such movement is accomplished without agitation of the mixing chamber and provides substantially uniform mixing of the test sample and the diluent thereby resulting in a diluted test sample.
The method of diluting the test sample for analysis in a sample analysis system includes aspirating, in sequence, selected predetermined amounts of test sample and diluent, moving the aspirated test sample and diluent back and forth along an axis that is inclined to the horizontal approximately 5 to 45 degrees. The method further includes separating the aspirated test sample and diluent with an air bubble. Separation of test sample and diluent is accomplished by aspirating the air bubble after aspirating one of the test sample and diluent and then aspirating the other of the test sample and diluent after the air bubble is aspirated.
The method further includes providing a mixing chamber with a volume that is at least two times greater than the volume of the aspirated test sample and diluent. This arrangement enables the air bubble that separates the test sample and diluent to migrate away from the test sample and diluent when the test sample and diluent are moved back and forth in the mixing chamber. The method also includes filling the hydraulic line with oil before aspiration of test sample, drawing the oil into a pump during aspiration of sample and diluent and reversing the movement of the oil toward the opening of the aspiration probe during dispensation of the mixed or diluted test sample from the aspiration probe.
The invention accordingly comprises the method and apparatus hereinafter described, the scope of the invention being indicated in the claims.